He was addressing the leaders of almost all the Middle Eastern churches gathered in the Italian port city of Bari to pray for peace in the region.
"There is also the danger that the presence of our brothers and sisters in the faith will disappear, disfiguring the very face of the region," the pope warned.
"For a Middle East without Christians would not be the Middle East.
"Indifference kills, and we desire to lift up our voices in opposition to this murderous indifference." Among those attending the ecumenical meeting in southern Italy are the patriarch Bartholomew of Constantinople, the spiritual leader of the eastern orthodox church, and metropolitan Hilarion of the Russian orthodox church which is powerful in Syria.
Patriarch Tawadros II is representing Egypt's orthodox Copts alongside six patriarch of eastern Catholic churches.
"We want to give a voice to those who have none, to those who can only wipe away their tears," the pope said ahead of talks with the church leaders.
"For the Middle East today is weeping, suffering and silent as others trample upon those lands in search of power or riches." Francis described the region as "the crossroads of civilisations and the cradle of the great monotheistic religions".
"Yet this region ... has been covered by dark clouds of war, violence and destruction, instances of occupation and varieties of fundamentalism, forced migration and neglect.
"All this has taken place amid the complicit silence of many." More than 350,000 people have been killed since Syria's brutal civil war began in 2011, with millions more displaced.
The percentage of Christians living in the Middle East has fallen from 20 percent before World War One to four percent today, according to the Pontifical Council for Promoting Christian Unity.
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